Post-translational modification of proteins through acetylation and deacetylation of lysine residues has a critical role in regulating cellular functions, making histone deacetylase an attractive biological target, particularly for the treatment of cancer. For example, WO 2007/095584 describes small molecule inhibitors or histone deacetylase having an esterase sensitive ester linkage. The presence of the esterase-sensitive linker provides an inhibitor which can achieve high local concentrations and reduced systemic toxicity.
Some small molecules that include labile covalent bonds can be unstable in aqueous solvents. For example, the presence of an esterase-sensitive linker may present difficulties with respect to preparation of a suitable formulation. As such, a need exists for stable pharmaceutical compositions of histone deacetylase inhibitors when the inhibitor has labile covalent bonds, such as those described in WO 2007/095584.